The first two major goals of this competing continuation proposal are to - - ) complete the analysis of the rich data set and 2) perform analyses of repository specimens -- collected during the three-year Postmenopausal Estrogen/Progestins Intervention (PEPI) randomized trial (N=875). PEPI was designed to compare the effect of placebo, unopposed estrogen and three regimens of estrogen and progestin on four primary (coronary heart disease risk factor) endpoints (high density lipoprotein cholesterol, systolic blood pressure, 2-hour post oral glucose load insulin and fibrinogen), bone mineral density and a number of secondary endpoints. Trial follow-up will end February 1994; its data will be edited and three principal manuscripts will be completed by August 1994, when funding ends. It is proposed that the PEPI research group (seven clinics and one coordinating center) complete approximately 20 additional papers based on the 36-month PEPI database and seven projects involving repository specimens (including mammography films). The third major goal is to conduct a three year post-trial (unblinded) follow-up of PEPI participants (expected N=700) to monitor and estimate the incidence of uterine and breast tissue changes and cancers, monitor changes in estrogen replacement therapy after unblinding women (at 36 months), and describe changes in the four primary endpoints and bone mineral density at 48, 60 and 72 months post-randomization. It is proposed that the current effective organization of the PEPI investigators be maintained. Each clinical center will be responsible for collaboration in scientific planning, analysis, and publication and for the recruitment and continued follow-up of women in the post-trial study. The coordinating center will continue to manage PEPI data; collaborate on and facilitate analyses and publications; collaborate with other investigators in developing study protocols and manuals, developing and monitoring quality control, and reporting; contract for centralized services including repository and follow-up specimen analysis; and actively participate in the administration of the study.